1. Field of the Invention
The present invention is concerned with certain novel 4-H-pyrrolo[3,2,1-ij]quinolin-1,2-diones and methods for their preparation. The invention is also concerned with the use of the novel compounds as inhibitors of aldose reductase and for the prevention and treatment of various diabetic complications including cataracts, neuropathy, retinopathy and nephropathy.
2. Description of the Prior Art
It has been established that high levels of polyols such as sorbitol and galactitol accumulate in certain tissues of the human body as, for example, in galactosemia and certain diabetic complications. The polyols are formed in the body by the enzymatic reduction of various hexoses such as glucose and galactose by the enzyme aldose reductase. In particular, the accumulation of the polyols in the lens and retina tissue of diabetic persons is responsible for the formation of cataracts and the concomitant loss of lens clarity. The investigations of Kenneth H. Gabby, New England Journal of Medicine 288 (16), 831-836 (1973) and references cited therein, and J. H. Kinoshita et al, Biochem. Biophys. Acta., 158, 472 (1968) and references cited therein have shown that inhibitors of aldose reductase effectively delay cataract formation in rats fed galactose. Thus, an agent which inhibits aldose reductase affords a potential means of preventing cataract formation in persons afflicted with diabetes and galactosemia. U.S. Pat. No. 3,821,383 discloses certain benzoquinoline acetic acids as useful in preventing or relieving diabetic complications. Science, 182 1146 (1973) discloses 1,3-dioxo-1H-benz[de]isoquinoline-2(3H) acetic acid (AY-22,284) as an aldose reductase inhibitor which effectively suppressed the formation of cataracts in galactosemic rats.